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Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle ProgressionChanges of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.
Document ID
20080014101
Acquisition Source
Johnson Space Center
Document Type
Conference Paper
Authors
Zhang, Ye
(NASA Johnson Space Center Houston, TX, United States)
Rohde, Larry H.
(Houston Univ.-Clear Lake Houston, TX, United States)
Emami, Kamal
(NASA Johnson Space Center Houston, TX, United States)
Casey, Rachael
(NASA Johnson Space Center Houston, TX, United States)
Wu, Honglu
(NASA Johnson Space Center Houston, TX, United States)
Date Acquired
August 24, 2013
Publication Date
January 1, 2008
Subject Category
Life Sciences (General)
Meeting Information
Meeting: 54th Annual Meeting of the Radiation Research
Location: Boston, MA
Country: United States
Start Date: September 21, 2008
End Date: September 25, 2008
Sponsors: Radiation Research Society
Distribution Limits
Public
Copyright
Other

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